Development of sugar-steroid compounds which have no steroidal activities themselves, but can be converted to the active forms by glucosidases which increase at the inflammatory site of rheumatism or the like have been reported by the research group of Merck & Co. J. Am. Chem. Soc. (1964), 86, 3903-4, FR3627 (1965) and GB1015396 (1965)!.
Several steroid derivatives aimed to reduce toxicity were also synthesized. For example, a sugar-steroid compound capable of specifically reaching the colon was reported (Japanese Patent Laid-open Publication, Sho60-501105 (WO8404041), J. Pham. Pharmacol. (1991), 43, 353-5, WO9415947 (disclosed on Jul. 21, 1994) and WO9322334 (disclosed on Nov. 11, 1993).
Although the unfavorable side-effects were somewhat reduced in the sugar-steroid compounds described in the aforementioned literatures, but still not sufficiently, requiring further improvement.
Inventors of the present invention actually synthesized glycosyl steroid derivatives wherein simple sugars or said simple sugars with hydroxyl groups thereof modified with acetyl groups were linked to steroids, and examined their pharmacological activities, confirming that side-effects of these derivatives were about the same as those of the aglycon steroids, and actually not sufficiently reduced probably because they might be readily hydrolyzed by glucosidases usually omnipresent within living body to release the aglycon steroids.